The cure for HIV could be as simple – well, almost — as a shot in the arm.

The full process, which researchers started testing in 2009, would look something like this: extract patient’s blood, eliminate HIV receptive gene on white blood cells, multiply those new cells, infuse billions of the cells into patient’s blood stream. And voila, the virus roams veins and arteries, lonely, with no receptors to bond with.

That process has a group of scientists hoping they might be on to something big.

But UCLA Medicine Professor Ronald Mitsuyasu is quick to remind his study patients that nothing is certain until the research is complete.

“The patients understand that it’s not a cure,” Mitsuyasu said. “That’s one of the clear things that I tell them at the outset – that it’s research and not designed to be a treatment, at least not at this point.”

Mitsuyasu is one of the lead investigators on a team of researchers studying the use of gene therapy as a way to cure HIV and AIDS. The study is funded by Sangamo BioSciences, Inc., a biotech company based in Richmond that developed the gene modification technology.

Mitsuyasu conducts his share of the study at the UCLA Center for Clinical AIDS Research and Education, where he serves as director. The study has several clinical trial locations across the country, but the research has been conducted primarily at UCLA and the University of Pennsylvania.

Sangamo founder and CEO Edward Lanphier told Richmond Confidential in September that a naturally occurring mutation of the gene for the HIV receptor CCR5, which scientists had seen in some HIV and AIDS patients, led Sangamo to the premise of their research: If the gene becomes dysfunctional, the virus is rendered impotent.

Once the patient’s blood is extracted and the white blood cells are isolated, scientists use a special enzyme called a zinc-finger protein to go in and edit out the CCR5 receptors on the virus-fighting T-cells. They then grow billions of these new cells in petri dishes and freeze them until the patient is ready for treatment.

The preparation process takes up to eight weeks, Sangamo Director of Corporate Communications Elizabeth Wolffe said. Mitsuyasu said transferring the modified cells back into the patient’s immune system using a standard IV line usually takes less than an hour.

Then, it’s wait and see.

The patients usually stay under a doctor’s supervision for a couple of hours after treatment to make sure they’re safe to return home, but so far there haven’t been any complications with the infusion process, Mitsuyasu said.

“We don’t expect any reactions because they’re the patient’s own cells, so they’re not like a foreign blood transfusion from somebody they don’t know,” he said. “It’s their own blood.”

The patients have to come in for weekly check-ups the first month after their dosage, he said. After they complete their weekly visit period, the scientists see them once a month for six months, and continue monitoring them for another year.

The hope is that patients’ bone marrow would begin producing the modified cells in place of their own cells, Mitsuyasu said. If that happens, the number of modified cells should increase and the patient’s viral load should drop.

Mitsuyasu said there are signs of correlation between gene-marked cells and viral load counts, but there’s not enough evidence for a cause-and-effect relationship quite yet.

A Sangamo scientist checks a treatment in a petri dish. Sangamo scientists say the first phase of their clinical trial showed their gene therapy approach to treating HIV is safe. (Photo courtesy of Sangamo)

One patient already demonstrated the anti-viral potential of the therapy.

The patient, who had been on standard anti-retroviral medication during the study, stopped taking the medication a year after the modified-gene injection.

The scientists saw an initial spike in the patient’s viral load and then a fall, back down to undetectable levels. Mitsuyasu said that rarely happens when an AIDS patient is taken off of anti-viral treatment, which meant he had enough of the modified cells present to prevent further cells from being infected.

“That gave rise to this discussion about whether this is a functional cure or not,” he said. “From my perspective, one patient doesn’t make a functional cure. But I think we’re on the right track.”

Mitsuyasu began researching the infection in 1981, when the epidemic gained notoriety and public fear of the virus began to spread.

“It’s been rewarding as well as frustrating, I think, just like any research,” he said. “The rewarding part is…there aren’t many people actually doing this kind of work, so anything that we find will be ultimately useful scientifically. I think the frustrating point is that one has to move cautiously whenever one works in anything that involves genetic therapy.”

Sangwei Lu, an infectious disease expert at the UC Berkeley School of Public Health who is not affiliated with the study, said using gene therapy to treat HIV and AIDS is promising, but there are many technical issues that need to be addressed, such as safe delivery methods.

“I don’t think there is anything in the clinical use yet because the safety issue has not been completely resolved,” Lu said. “Obviously, if you want to treat anything, you want to do no harm.”

The Federal Drug Administration has yet to approve the sale of a gene therapy product, according to the Human Genome Project’s website. The technique can be used to treat several kinds of diseases, including cancers and herpes simplex, but the HGP notes patients can experience a short-lived effect, negative immune response, and difficulty with diseases that span several different genes.

Sangamo representatives said in a public statement in September that the phase one clinical study proved that the unique approach to fighting HIV and AIDS is safe.

Lanphier told Richmond Confidential the week before publicizing their clinical trial results that the industry’s general reception of his company’s work has been positive, despite the long history of criticisms aimed at gene therapy.

“When we presented the very first clinical results earlier this year, many of the comments were that this is the most exciting approach to a functional cure to HIV,” he said. “It’s not as a treatment for HIV, but as a potential functional cure for HIV.”

Present-day treatment for the infection involves an expensive cocktail of anti-viral medications that usually cost anywhere from $10,000 to $20,000 a year, Mitsuyasu said. He estimates the cost of gene therapy treatment would fall in the same range, but it would be less expensive over a lifetime because it would only need to be administered once.

But that doesn’t mean there will necessarily be an end to anti-viral treatment. Ultimately, Mitsuyasu said, patients will be given a choice between gene modification and anti-virals.

“You don’t want to do things that put people at risk, particularly people with HIV, who are asymptomatic, who could live a normal life with HIV medication, but it’s just inconvenient,” he said.

Marcy Darnovsky, the associate executive director of the Center for Genetics and Society, a Berkeley-based nonprofit that lobbies for safe and responsible use of gene modification, said gene therapy needs to be greeted less as “the holy grail” of modern science and more as a promising technique that still has some kinks to work out.

“It almost sounds curmudgeonly to raise that now because there’s this exciting thing on the horizon,” she said. “But I think it’s really important to have this all out at the beginning before we get carried away with these powerful new techniques.”

Mitsuyasu said scientists always run the risk of cells traveling to unintended destinations when the modified genes are delivered back into a patient’s immune system.

“When you inject something into a patient, you really don’t know where it’s going to go and where it’s going to integrate and what side effects it might have,” he said.

The difference between Sangamo’s approach and gene therapy treatments for diseases such as cancer, Mitsuyasu said, is that HIV is blood-borne, so when the modified cells are injected, they are already exactly where they need be. But he said the team’s finding shows that the therapy has been most effective when the cells migrate to the digestive system, where scientists presume the virus first enters the immune system and where most of the replication takes place.

Mitsuyasu said the researchers are making strides but, in the long-term, scientists in general need to explore an HIV vaccination that will bring the fight against AIDS full circle.

A combination of a vaccine and gene therapy would be the best approach and eliminate the need for daily dosage of anti-virals, he said.

“If we can protect cells against HIV, further HIV infection, and also boost up immunity against HIV, we’d have a two-pronged approach in which the host could try to control their virus without medications,” he said.

Lu said she doesn’t see gene therapy as the first step because it doesn’t provide the complete control over a disease that a vaccine would.

“You can treat infected people, but you will not completely stop the spread of diseases,” she said.

As the researchers begin the second phase of their clinical trial, Mitsuyasu said the scientists will have to demonstrate the treatment has some significant biological and clinical impact.

While he’s careful not to pin gene therapy as the cure for AIDS, Mitsuyasu said he hopes that decades of research and encouraging data from Sangamo’s studies will be enough to convince the regulatory agencies that the technique is a viable treatment for the disease.

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